Pharmaceutical compositions containing an ipratropium salt and a betamimetic

Abstract

Pharmaceutical composition comprising: (a) an ipratropium salt; and (b) a betamimetic, and their use in treating inflammatory or obstructive diseases of the respiratory tract in a patient in need of such treatment.

We claim:  
     
         1 . A pharmaceutical composition comprising: 
 (a) an ipratropium salt; and    (b) a betamimetic.    
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the ipratropium salt is a salt formed with HBr, HCl, HI, monomethylsulfuric acid ester, methanesulfonic acid, methylsulfate, or p-toluenesulfonic acid.  
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the betamimetic is a salt formed with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid, 1-hydroxy-2-naphthalenecarboxylic acid, or maleic acid.  
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the betamimetic is a salt of salmeterol or formoterol.  
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the betamimetic is selected from salmeterol hydrochloride, a salmeterol sulfate, or salmeterol xinafoate.  
     
     
         6 . The pharmaceutical composition according to  claim 4 , wherein the weight ratio of the ipratropium salt to the betamimetic is in a range from about 1:30 to 400:1.  
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the betamimetic is selected from formoterol hydrochloride, formoterol sulfate, or formoterol fumarate.  
     
     
         8 . The pharmaceutical composition according to  claim 1 , wherein the weight ratio of the ipratropium salt to the betamimetic is in a range from about 1:35 to 300:1.  
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is in a form suitable for inhalation.  
     
     
         10 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is an inhalable powder, a propellant-containing metering aerosol, or a propellant-free inhalable solution or suspension.  
     
     
         11 . The pharmaceutical composition according to  claim 9 , wherein the pharmaceutical composition further comprises a suitable physiologically acceptable excipient selected from the group consisting of: monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, and salts.  
     
     
         12 . The pharmaceutical composition according to  claim 10 , wherein the pharmaceutical composition further comprises a suitable physiologically acceptable excipient selected from the group consisting of: monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, and salts.  
     
     
         13 . The pharmaceutical composition of  claim 11 , wherein the excipient has a maximum average particle size of up to 250 μm.  
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein the excipient has a maximum average particle size of up to 250 μm.  
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the excipient has a maximum average particle size of between 10 μm and 150 μm.  
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the excipient has a maximum average particle size of between 10 μm and 150 μm.  
     
     
         17 . A capsule containing a pharmaceutical composition according to  claim 1  in the form of an inhalable powder.  
     
     
         18 . A capsule containing a pharmaceutical composition according to  claim 2  in the form of an inhalable powder.  
     
     
         19 . A capsule containing a pharmaceutical composition according to  claim 3  in the form of an inhalable powder.  
     
     
         20 . A capsule containing a pharmaceutical composition according to  claim 4  in the form of an inhalable powder.  
     
     
         21 . A capsule containing a pharmaceutical composition according to  claim 5  in the form of an inhalable powder.  
     
     
         22 . A capsule containing a pharmaceutical composition according to  claim 6  in the form of an inhalable powder.  
     
     
         23 . A capsule containing a pharmaceutical composition according to  claim 7  in the form of an inhalable powder.  
     
     
         24 . A capsule containing a pharmaceutical composition according to  claim 8  in the form of an inhalable powder.  
     
     
         25 . A pharmaceutical composition consisting essentially of: 
 (a) an ipratropium salt; and    (b) a betamimetic,    wherein the pharmaceutical composition is in the form of an inhalable powder.    
     
     
         26 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is a propellant-containing inhalable aerosol and the ipratropium salt and the betamimetic are in dissolved or dispersed form.  
     
     
         27 . The pharmaceutical composition according to  claim 26 , wherein the propellant-containing inhalable aerosol comprises a propellant gas selected from hydrocarbons and halohydrocarbons.  
     
     
         28 . The pharmaceutical composition according to  claim 26 , wherein the propellant-containing inhalable aerosol comprises a propellant gas selected from the group consisting of: n-propane; n-butane; isobutane; and chlorinated and/or fluorinated derivatives of methane, ethane, propane, butane, cyclopropane, and cyclobutane.  
     
     
         29 . The pharmaceutical composition according to  claim 26 , wherein the propellant gas is TGI34a, TG227, or a mixture thereof.  
     
     
         30 . The pharmaceutical composition according to  claim 26 , further comprising at least one of a cosolvent, stabilizer, surfactant, antioxidant, lubricant, or means for adjusting the pH of the composition.  
     
     
         31 . The pharmaceutical composition according to  claim 29 , further comprising at least one of a cosolvent, stabilizer, surfactant, antioxidant, lubricant, or means for adjusting the pH of the composition.  
     
     
         32 . The pharmaceutical composition according to  claim 30 , further comprising at least one of a cosolvent, stabilizer, surfactant, antioxidant, lubricant, or means for adjusting the pH of the composition.  
     
     
         33 . The pharmaceutical composition according to  claim 31 , further comprising at least one of a cosolvent, stabilizer, surfactant, antioxidant, lubricant, or means for adjusting the pH of the composition.  
     
     
         34 . The pharmaceutical composition according to  claim 1 , wherein the amount of the ipratropium salt and the betamimetic is up to 5 wt. % of the pharmaceutical composition.  
     
     
         35 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is propellant-free inhalable solution or suspension that further comprises a solvent selected from water, ethanol, or a mixture of water and ethanol.  
     
     
         36 . The pharmaceutical composition according to  claim 35 , wherein the pH is between 2 and 7.  
     
     
         37 . The pharmaceutical composition according to  claim 36 , wherein the pH is between 2and 5.  
     
     
         38 . The pharmaceutical composition according to  claim 35 , wherein the pH of the pharmaceutical composition is adjusted by means of one or more acids selected from the group consisting of: hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid, and propionic acid.  
     
     
         39 . The pharmaceutical composition according to  claim 35 , further comprising other co-solvents or excipients.  
     
     
         40 . The pharmaceutical composition according to  claim 38 , further comprising other co-solvents or excipients.  
     
     
         41 . The pharmaceutical composition according to  claim 39 , wherein the co-solvent is selected from the group consisting of alcohols, glycols, polyoxyethylene alcohols, and polyoxyethylene fatty acid esters.  
     
     
         42 . The pharmaceutical composition according to  claim 39 , wherein the co-solvent is selected from the group consisting of: isopropyl alcohol, propylene glycol, polyethylene glycol, polypropylene glycol, glycol ether, and glycerol.  
     
     
         43 . The pharmaceutical composition according to  claim 39 , wherein the excipient is selected from the group consisting of: surfactants, stabilizers, complexing agents, antioxidants, preservatives, flavorings, pharmacologically acceptable salts, and vitamins.  
     
     
         44 . The pharmaceutical composition according to  claim 43 , wherein the excipient is selected from the group consisting of: edetic acid, a salt of edetic acid, ascorbic acid, vitamin A, vitamin E, tocopherols, cetyl pyridinium chloride, benzalkonium chloride, benzoic acid, and benzoate salts.  
     
     
         45 . A method of treating inflammatory or obstructive diseases of the respiratory tract in a patient in need of such treatment, the method comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition according to one of  claims 1  to  12 .  
     
     
         46 . The method according to  claim 45 , wherein the pharmaceutical composition is administered to the patient by inhalation after nebulizing the pharmaceutical composition into an inhalable aerosol using an energy-operated free-standing or portable nebulizer that produces inhalable aerosols by means of ultrasound or compressed air.  
     
     
         47 . A pharmaceutical composition consisting essentially of: 
 (a) an ipratropium salt;    (b) a betamimetic;    (c) a solvent;    (d) benzalkonium chloride; and    (e) sodium edetate.    
     
     
         48 . A pharmaceutical composition consisting essentially of: 
 (a) an ipratropium salt;    (b) a betamimetic;    (c) a solvent; and    (d) benzalkonium chloride.    
     
     
         49 . A kit comprising one or more unit dosage containers containing a pharmaceutical composition, each unit dosage container containing a pharmaceutical composition comprising: 
 (a) an ipratropium salt; and    (b) a betamimetic,    each optionally together with a pharmaceutically acceptable excipient.    
     
     
         50 . The kit according to  claim 49 , further comprising instructions with directions for using the kit.  
     
     
         51 . The kit according to  claim 49 , wherein the betamimetic is a salt of salmeterol or formoterol.  
     
     
         52 . The kit according to  claim 49 , wherein the betamimetic is selected from salmeterol hydrochloride, a salmeterol sulfate, or salmeterol xinafoate.  
     
     
         53 . The kit according to  claim 49 , wherein the betamimetic is selected from formoterol hydrochloride, formoterol sulfate, or formoterol fumarate.  
     
     
         54 . A kit comprising: 
 (a) a first container containing a first pharmaceutical formulation comprising an ipratropium salt; and    (b) a second container containing a second pharmaceutical formulation comprising a comprising a betamimetic,    each container each optionally further containing a pharmaceutically acceptable excipient.    
     
     
         55 . The kit according to  claim 54 , further comprising instructions with directions for using the kit.  
     
     
         56 . The kit according to  claim 54 , wherein the betamimetic is a salt of salmeterol or formoterol.  
     
     
         57 . The kit according to  claim 54 , wherein the betamimetic is selected from salmeterol hydrochloride, a salmeterol sulfate, or salmeterol xinafoate.  
     
     
         58 . The kit according to  claim 54 , wherein the betamimetic is selected from formoterol hydrochloride, formoterol sulfate, or formoterol fumarate.